Dehydrated hydrogels

ABSTRACT

A method of producing a dehydrated hydrogel comprises dispensing fibers into an aqueous solution of a hydrogel precursor material incorporating a plasticiser, the fibers incorporating cations which are capable of cross-linking said precursor material to form a hydrogel, and freeze drying the mixture thus produced to provide a dehydrated hydrogel which incorporates said fibers, the dehydrated hydrogel being cross-linked by said cations.

The present invention relates to dehydrated hydrogels which are usefulin the treatment of wounds.

A hydrogel is a cross-linked macromolecular network swollen with wateror biological fluids. A dehydrated hydrogel is a cross-linkedmacro-molecular network that will swell to form a hydrogel upon contactwith water or biological fluids. Due to their ‘dehydrated’ condition,dehydrated hydrogels are easy to store and transport. In addition, whenapplied in the dry state to a wound they behave as superabsorbentmaterials.

Our co-pending PCT Application No. PCT/GB95/02543 (WO-A-96/13285)discloses a method of producing a dehydrated hydrogel comprisingdispersing fibres into an aqueous solution of a hydrogel precursormaterial incorporating a plasticiser, the fibres incorporating cationswhich are capable of cross-linking said precursor material to form ahydrogel, and evaporating water to produce a dehydrated hydrogel whichincorporates said fibres, the dehydrated hydrogel being cross-linked bysaid cations.

According to the present invention there is provided a method ofproducing a dehydrated hydrogel comprising dispersing fibres into anaqueous solution of a hydrogel precursor material incorporating aplasticiser, the fibres incorporating cations which are capable ofcross-linking said precursor material to form a hydrogel, and freezedrying the mixture thus produced to provide a dehydrated hydrogel whichincorporates said fibres, the dehydrated hydrogel being cross-linked bysaid cations.

Therefore in the method of the invention water is evaporated from theadmixture of hydrogel precursor material, fibres and plasticiser by afreeze drying procedure. Known conditions for freeze drying may beemployed. Thus, for example, the admixture may be frozen below −10° C.to form a solid product (e.g. a sheet) in which the hydrogel precursoris embedded in ice. The frozen mixture may then be subjected to a highvacuum so as to allow conversion of water from solid ice to water vapour(without passing through an intermediate liquid phase). The freezedrying procedure may be carried out using an Edwards freeze dryingmachine.

As a result of the method of the invention, the delicate pore structureof the frozen mixture is preserved and the final product (dehydratedhydrogel) is porous and highly absorbent.

The dehydrated hydrogel produced by the method of the invention may bein the form of a film having a thickness of, for example, 20 microns to10 mm.

The dehydrated hydrogels produced by the method of the invention have anumber of advantages. In particular, the presence of the fibres impartsstrength and dimensional stability to the dehydrated hydrogel.Furthermore films of the dehydrated hydrogels have the property ofswelling in only the thickness dimensions and not in the other twodimensions (as compared to films of conventional dehydrated hydrogelswhich swell in all three dimensions).

Typically, the dehydrated hydrogels will comprise (based on the totalweight of the fibres, polymer forming the hydrogel, and plasticiser,i.e. excluding water and other components) 15 to 40% by weight offibres, 10 to 35%, and 5 to 75% plasticiser. More preferably the fibresand polymer together provide about 40-60% ideally about 50% by weight onthe same weight basis so that correspondingly the plasticiser provides60-40%, ideally about 50%. Generally the amount of fibres will exceedthe amount of polymer. For example the weight ratio may be 1.5-3:1.Typically the dehydrated hydrogel will contain less than 50% by weightof water, ideally less than 20%, based on the total weight of thedehydrated hydrogel.

Examples of hydrogel precursor material which may be used include sodiumalginate, sodium carboxymethyl cellulose, sodium pectinate, sodiumO-carboxymethyl chitosan (OCC), sodium N,O-carboxymethyl chitosan(NOCC), sodium polyacrylate, and naturally occurring gums and syntheticpolymers containing pendant carboxylic acid groups (hummectants).

The hydrogel precursor may consist wholly or partially of Ace Mannan (orother component of Alloe Vera) which is a natural polymer known toaccelerate healing of wounds. The Ace Mannan may, for example, provideup to 80% of the matrix. The Ace Mannan may be clinical grade materialobtainable from Carrington Laboratories, Dallas, Tex., USA.

The fibres which are used contain a di- or higher valent cation which iseffective for cross-linking the hydrogel. Examples of suitable cationsinclude Ca^(2°), Zn²⁺, and cations which also act as enzyme cofactors.Particular preferred examples of fibres which may be used are calciumalginate fibres. The fibres will generally have a length of 1 to 80 mmand a thickness of 10 to 50 microns.

The fibres may be such that they absorb water from the aqueous solutionof the hydrogel precursor material during manufacture of the dehydratedhydrogel.

Examples of suitable plasticisers include glycerol, polyethylene glycol,sorbitol and similar sugars, and pluronic type PEO/PPO polymers.

In a typical method of preparing a dehydrated hydrogel in accordancewith the invention, the fibres, polymer and plasticiser in theirrelative requisite amounts are admixed with water such that the fibres,polymer and plasticiser together provide less than 5% by weight (e.g.less than 3%, e.g. 2%) of the resultant mixture. After thorough mixing,the dispersion may be cast to an appropriate thickness and freeze driedto give a dehydrated hydrogel product containing less than 50% water,more usually 20% or less.

Dehydrated hydrogels have a number of advantages. In particular whenapplied to the wounds (e.g. donor sites, abrasions, dermabrasions,surface wounds with high exudate or wide savings in exudate levels) theyare capable of absorbing large amounts of exudate, e.g. up to 30 timestheir own weight, thereby rehydrating to form a hydrogel. If thedehydrated hydrogel is in the form of a film, it is found that the filmswells in the thickness dimension without substantial swelling in theother two dimensions. Upon sufficient absorption of exudate, the film iscapable of dissolving. The product of the invention is more absorbentthan current commercial hydrogels, and is also light and easy topackage.

Dehydrated hydrogels produced in accordance with the method of thisinvention may be laminated to hydrophilic films which have an increasedbreathability in the presence of liquid water as compared to moisturevapour alone. The use of such a film over the dehydrated hydrogel (i.e.on the side remote from the wound) ensures that water is vented from thedehydrated hydrogel through the film. Therefore the dissolution of thehydrogel may be controlled.

Typically the breathable film will be of a material which, as a 50micron film, has an MVTR in the presence of moisture vapour alone of6,000 to 10,000 g m⁻² 24 hr⁻¹ as measured by ASTM E96B and an MVTR inthe presence of liquid water (as measured by ASTM E96BW) of 6,000 to10,000 g m⁻² 24 hr⁻¹. Typically the breathable film will have athickness of 30-70 microns, more preferably 40-60 microns, e.g. about 50microns.

The breathable film may for example be of polyurethane. Suitable filmsare available from Innovative Technologies Limited under thedesignations IT325, IT425 and IT625.

If desired, the dehydrated hydrogel may incorporate an active agent(e.g. an antimicrobial material) for delivery to a wound.

The invention will be further described by the following non-limitingExamples.

EXAMPLE 1

3 Grams of MF1-2B fibres (calcium alginate fibres available fromInnovative Technologies) were cut to about 10 mm length. The fibres weremixed with 2 g of sodium alginate powder (protonol LF10/6OLS, exPronova), 5 g of glycerol and 1000 ml of water. The mixture was thenplaced into a stainless steel dish (23 cm×23 cm) to form a gelpre-cursor solution. The solution was then placed in a freezer (T<−10°C.) so that the gel pre-cursor frozen to form a solid ice. The dish wasthen taken immediately to a freeze frying machine (Edwards) to preparethe freeze dried pad and dried over a period of about 20 hours.

The resultant product was a dehydrated hydrogel capable of absorbing atleast 20 grams of normal saline for a 10 cm×10 cm pad.

EXAMPLE 2

3Grams of MF1-21B fibres (calcium/sodium alginate fibres available fromInnovative Technologies) were cut to about 50 mm length. The fibres weremixed with 3 g of sodium alginate powder (Protonol LF10/60, ex Pronova),6 g of glycerol and 1000 ml of water. The mixture was then placed into astainless steel dish (23 cm×23 cm) to form a gel pre-cursor solution.The solution was then placed in a freezer (T<−10° C.) so that the gelpre-cursor frozen to form a solid ice. The dish was taken immediately toa freeze drying machine (Edwards) to prepare the freeze dried pad anddried over a period of about 20 hours.

The resultant product was a dehydrated hydrogel capable of absorbing atleast 20 grams of normal saline for a 10 cm×10 cm pad.

What is claimed is:
 1. A method of producing a dehydrated hydrogelcomprising dispersing fibres into an aqueous solution of a hydrogelprecursor material incorporating a plasticiser, the fibres incorporatingcations which are capable of cross-linking said precursor material toform a hydrogel, and freeze drying the mixture thus produced to providea dehydrated hydrogel which incorporates said fibres, the dehydratedhydrogel being cross-linked by said cations.
 2. A method as claimed inclaim 1 wherein the hydrogel precursor material is selected from sodiumalginate, sodium carboxymethyl cellulose, sodium pectinate, sodiumO-carboxymethyl chitosan (OCC), sodium N,O-carboxymethyl chitosan(NOCC), sodium polyacrylate, and naturally occurring gums and syntheticpolymers containing pendant carboxylic acid groups (hummectants).
 3. Amethod as claimed in claim 1 wherein the fibres contain Ca²⁺, Zn²⁺and/or cations which also act as enzyme cofactors.
 4. A method asclaimed in claim 1 wherein the fibres are calcium alginate fibres.
 5. Amethod as claimed in claim 2 wherein the hydrogel precursor material issodium alginate.
 6. A method as claimed in claim 5 wherein the fibresare calcium alginate fibres.
 7. A method as claimed in claim 1 whereinthe dehydrated hydrogel comprises 15 to 40% by weight of fibres, 10 to35% by weight of polymer forming the hydrogel and 5 to 75% by weight ofplasticiser, the percentages being based on the total weight of thefibres, polymer forming the hydrogel, and the plasticiser.
 8. A methodas claimed in claim 1 wherein the ratio by weight of the fibres to thatof the polymer is 1.5-3:1.
 9. A method as claimed in claim 1 wherein thedehydrated hydrogel contain less the 20% by weight of water based on thetotal weight of the dehydrated hydrogel.
 10. A method as claimed inclaim 1 wherein the fibres have a length of 1 to 80 mm and a thicknessof 10 to 50 microns.